• Aj ay Kumar Singh• Ar t i Elhence Agar wal• Depar t ment of Opht halmology• King Geor ge‘s Medical Univer sit y,
INTRODUCTION • Dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance and tear film instability with potential damage to the ocular surface.* • It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface. * *2007 Report of the Dry Eye Work Shop (Ocul Surf 2007;5:65-204)
• According to the International task force guidelines for diagnosis and treatment of dry eye1 X Dry eye disease Dysfunctional Tear Syndrome (DTS)1. Behrens A, Doyle JJ, Stern L, et al. Dysfunctional tear syndrome. A Delphi approach to treatment recommendations. Cornea. 2006;25:90-97.
SOME RELATED TERMS ... • Keratoconjunctivitis Sicca Any eye with some degree of dryness • Xerophthalmia Dry eye associated with Vitamin A deficiency • Xerosis Extreme ocular dryness and keratinization associated with severe conjunctival cicatrisation
Dry eye is a disturbance of Lacrimal Function Unit(LFU) • Tearing apparatus – Production- lacrimal gland – Clearance- lacrimal passages • Ocular surface – Conjunctiva – Cornea • Eyelids • Sensory and motor nerves
Tear secretion• Lacrimal gland – Producing the watery part of the tear film called the aqueous.• Meibomian glands – Producing lipids which keep the tear film from evaporating.• Goblet cells of the conjunctiva – Producing mucin which allows the wetting of the ocular surface as well as stabilizes the tear film.
Tear and the Tear Film• Function : – Maintain a smooth corneal surface – Moistens cornea and conjunctiva – Lubrication of pre-ocular surface and lids – Transfer of oxygen to cornea from ambient air – Prevents infection
Healthy Tears • A complex mixture of proteins, mucin, and electrolytes: • Antimicrobial proteins: • Lysozyme, lactoferrin • Growth factors & suppressors of inflammation: • EGF, IL-1RA • Soluble mucin 5AC secreted by goblet cells for viscosity • Electrolytes for proper osmolarityStern et al. In: Dry Eye and Ocular Surface Disorders. 2004., Image adapted from: Dry Eye and Ocular Surface Disorders. 2004
Tears in Chronic Dry Eye• Decrease in many proteins• Decreased growth factor concentrations• Altered cytokine balance promotes inflammation• Soluble mucin 5AC greatly decreased • Due to goblet cell loss • Impacts viscosity of tear film• Proteases activated• Increasedet electrolytes Vis Sci. 2001.Zhao et al. Cornea. 2001.Ogasawara et al. Graefes Arch Clin Exp Ophthalmol. 1996. Solomon al. Invest Ophthalmol Image adapted from: Dry Eye and Ocular Surface Disorders. 2004.
•Tear film disorders –Aqueous tear deficiency –Lipid tear deficiency –Mucoprotein deficiency –Kinetic disorders of lacrimal fluid
Ocular surface disorders •Corneal and conjunctival lesions: –Squamous epithelization type –Limbal stem cell deficiency type
THE HEALTHY EYE NORMAL TEARING DEPENDS ON A NEURONAL FEEDBACK LOOP Secretomotor Nerve Impulses Tears Support and Maintain Ocular Surface Lacrimal Glands Ocular Surface Neural Stimulation Stern et al, Cornea. 1998:17:584
DRY EYE DISEASE: An Immune-MediatedInflammatory Disorder INFLAMMATION DISRUPTS NORMAL NEURONAL CONTROL OF TEARING. Interrupted Secretomotor Nerve Impulses Lacrimal Glands: • Neurogenic Inflammation • T-cell Activation • Cytokine Secretion into Tears Inflame Ocular Tears Surface Cytokines Disrupt Neural Arc Stern et al, Cornea. 1998:17:584
CLASSIFICATION• International Dry Eye Workshop (DEWS): – 3-part classification • Etiology • Mechanism • Severity• Updated by National Eye Institute on basis of etiopathogenesis: – Aqueous deficiency state – Evaporative state
– Low blink rate • Parkinson’s disease– Disorder of eye lids and lid/globe congruity • Lid palsy • Exophthalmos
• Dry eye in contact lens users: – Contact lens dynamics: • Alterations in the pre corneal tear film (PCTF) • Reduction in corneal sensations • Corneal hypoxia • Reduced blinking • Thermal destabilisation.
Dry eye severity 1 2 3 4levelDiscomfort, severity Mild and/or episodic; Moderate episodic or Severe frequent or Severe and/or& frequency occurs under chronic, stress or no constant without disabling and environmental stress stress stress constantVisual symptom None or episodic Annoying and/or Annoying, chronic Constant and/or mild activity-limiting and/or constant, possibly disabling fatigue episodic limiting activityConjunctival None to mild None to mild +/– +/++injectionConjunctival None to mild Variable Moderate to marked MarkedstainingCorneal staining None to mild Variable Marked central Severe punctate(severity/location) ErosionsCorneal/tear signs None to mild Mild debris, ↓ Filamentary keratitis, Filamentary keratitis, meniscus mucus clumping, mucus clumping, ↑ tear debris ↑ tear debris,
Triggers of Dry Eye DiseaseEnvironment, Rheumatoid ArthritisMedications, Lupus,Contact Lens, Irritation Inflammation Sjögren’s,Surgery Graft vs Host Disease Tear Deficiency/ Menopause, Meibomian Gland Instability Disease Symptoms of Ocular Surface Disease
Increases significantly with age Prevalence of dry eye symptoms by age 20 15 Prevalence (%) 10 5 0 Age 48-59 Age 60-69 Age 70-79 Age 80-91 Beaver Dam study Arch Oph 2000, 118:1264-1268
More in women Prevalence of dry eye symptoms by age and sex 30 20Prevalence (%) Women 10 0 Men Age 48- Age 60- Age 70- Age 80- 59 69 79 91 Beaver Dam study Arch Oph 2000, 118:1264-1268
CLINICAL MANIFESTATION Irritation Redness Burning/ Stinging Tearing Contact lens intolerance Increased frequency of blinking Itchy eyes foreign body sensation Blurred vision Photophobia (less frequent symptom) Thick sticky mucous discharge
– Worsening of symptoms: As day progresses After prolonged reading, working on computers In windy or air-conditioned environments many symptoms are similar to those seen in more common conditions - mild blepharitis, conjunctival infections, allergies & refractive errors
• Coexisting connective tissue disease, rheumatoid arthritis, thyroid abnormalities• History of prolonged medication – topical – systemic• History of prolonged dryness of oral cavity, repeated mucosal ulcers
ON EXAMINATION• Eye lids: Lid margin Eye lashes Infections Crusting/keratinisation Lid closure• Conjunctival sac: Decreased tear meniscus Increased debris in the tear film Mucous discharge• Bulbar conjunctiva: dry lustreless Muddy Bitot’s spots hyperaemia
• Cornea: – Dry lustreless, hazy look – Irregular surface – Superficial punctuate keratitis (Fluorescein staining may be helpful) – filaments – Ulcers/scars in severe cases
• Clinical presentation can vary in severity Mild Severe Slitlamp Fluorescein Dye Stain
• Tear secretion assessment • Schirmer’s test – Schirmer’s I : Conjunctival stimulation – Schirmer’s II : Nasal stimulation – Schirmer’s III : Retinal stimulation – Jones’ modification : Basal secretion (2mts. After LA) • Phenol red thread test- more reliable than Schirmer’s test
Schirmer TestUpto 30 years : 20 mm/5 min31-50 years : 13 mm/5 min51 and above : 10mm/5 min< 5 mm/5 min- dry eye<3 mm/5 min- if topical anesthesia is used. Zappia RJ, Am.J.Ophthol 1972; 74: 160-162
Impression Cytology• Used for grading the severity• Has also been used as a prognostic indicator in evaluating efficacy of therapeutic measures• Features: – Relatively larger cell size – squamous metaplasia – inflammatory cells – decrease in goblet cell densities
Potential Severe Consequences of UntreatedDry Eye Disease Sterile Melting Bacterial Keratitis
MANAGEMENT• Goals of management: – Establish the diagnosis. – Differentiate from other causes of similar symptoms. – Establish presence/absence of limbal cell deficiency. – Decide appropriate therapy. • To relieve symptoms • To prevent complications – Educate patient / relatives about nature of disease and its management.
• Elimination/avoidance of exacerbating factors which • Decrease tear production • Increase tear evaporation – Humidification of rooms – Avoidance of dusty/smoky rooms – Breaks between prolonged computer use – Lowering the computer monitor below eye level – Low water content contact lenses for Shorter duration at a time. – Blinking exercises*• *Wolkoff P et al. Occup Environ Med 2005;62:4-12
• Tear supplementation – Ideal tear supplement should • Be preservative free • Contain K+, HCO3- and other electrolytes • Have a polymeric system to increase its viscosity, hence retention time • Have neutral to slightly alkaline pH • Have osmolarity- 181-354 mOsm/L
• Tear retention – Punctal occlusion: Temporary and Permanent. • Absorbable – collagen or polymers – Duration- 1 week- 6 months • Nonabsorbable – Silicone or acrylic – Moisture chamber spectacles – Contact lenses • Severe dry eye – Retain tear film – Promote ocular surface healing – Tarsorrhaphy
• Biological tear substitutes – Autologous serum tears1 – Can be stored frozen for 3-6 months – Autologous platelet rich plasma2 – Salivary gland autotransplantation3• 1. Geerling G et al. Br J Ophthalmol 2004;88:1467-74.• 2. Alio JL. Journal of Refractive Surgery 2007;23.• 3. Geerling G et al. Ophthalmology1998;105:327-35.
• Anti-inflammatory therapy – Topical cyclosporine • Only pharmacological agent approved by FDA for treatment of dry eye • Reduces conjunctival IL-6 levels, activated lymphocytes, inflammatory and apoptotic markers • Increases conjunctival goblet cell number – Corticosteroids • Recommended only for short-term use – Systemic medications • Oral tetracyclines (used for anti-inflammatory action) – Decrease matrix metalloproteinase activity and production of cytokines such as IL-1 and TNF-ɑ
• Essential fatty acids – Reduce inflammation – Alter the composition of meibomian lipids • Omega-3 fatty acids – Inhibit the synthesis of proinflammatory mediators (PGs and LTs) – Block the production of IL-1 and TNF-ɑ • Omega-6 fatty acids – Precursors of proinflammatory mediators (PGE2 and LTB4) • High Ω-6: Ω- 3 ratio is associated with greater risk for dry eye disease*• *Miljanovic B et al. Am J Clin Nutr 2005;82:887-93.
SUMMARY• Eliminating the etiological factors• Tears replacement therapy• Maintain moisture in the eyes• Increasing the tear secretion• Immune inhibition therapy• Re-establish the tear film• Other supporting treatment
CARRY HOME MESSAGE… • Methodical approach to diagnosis. • Do not miss subtle clinical signs. • Carefully plan the line of treatment. • Irrespective of cause of dry eye- immunomodulation + tear replacement. • Educate the patient and family members about the dilemmas in management.